Absence of synergistic activity between ampicillin and vancomycin against highly vancomycin-resistant enterococci.

The emergence of clinical enterococcal isolates resistant to both ampicillin and vancomycin is a cause of great concern, as there are few therapeutic alternatives for treatment of infections caused by such organisms. We evaluated the effects of the combination of ampicillin with vancomycin against vancomycin-resistant clinical enterococcal isolates. Using both the checkerboard technique and time-kill curves, we examined 28 strains of enterococci (17 Enterococcus faecalis and 11 Enterococcus faecium strains) with different levels of resistance to vancomycin. Of these, 15 strains were also highly gentamicin resistant, and 9 demonstrated resistance to ampicillin. Only seven strains of E. faecalis were inhibited synergistically by the combination of vancomycin with ampicillin, and even then, the concentrations of vancomycin at which synergism was demonstrated were above levels achievable in serum. None of the ampicillin-resistant isolates (all E. faecium) were inhibited synergistically at any concentration of the drugs. In no instance was bactericidal synergism observed, and in most cases the combination resulted in less killing than with ampicillin alone. Antagonism was not observed at clinically relevant concentrations. The results of this study suggest that the combination of vancomycin with ampicillin has little to offer against these emerging pathogens.     

新生儿重症监护病房多重耐药菌筛查及耐药性分析

目的分析新生儿重症监护病房（NICU）住院患儿多重耐药菌的定植状况以及耐药特点,为预防和控制多重耐药菌在院内的传播及临床合理用药提供科学依据。 方法对2018年5月1日至10月31日期间在广西壮族自治区妇幼保健院NICU住院患儿176例,入院1 h内采集肛拭子进行定植菌筛查。筛查阳性者,进行耐药性分析,了解NICU住院患儿细菌定植及耐药情况。采用χ²检验比较不同分娩方式患儿中细菌培养结果及不同日龄患儿细菌分离率的差异。 结果在23例患儿标本中检测出多重耐药菌,多重耐药菌定植率13.1%（23/176）,日龄<3 d新生儿多重耐药菌筛查阳性率低于日龄3~28 d的新生儿,差异具有统计学意义（χ²=4.099,P=0.043）。其中23株多重耐药细菌包括：11株产超广谱β-内酰胺酶（ESBLs）肠杆菌,10株耐万古霉素肠球菌（VRE）,2株耐甲氧西林金黄色葡萄球菌（MRSA）。11株产ESBLs肠杆菌对氨苄西林、哌拉西林、头孢唑啉、头孢呋辛、头孢曲松、庆大霉素耐药率达100%;10株VRE对万古霉素、青霉素、氨苄西林耐药率达100%,对替考拉宁和利奈唑胺完全敏感。2株MRSA除对万古霉素、替考拉宁和利奈唑胺完全敏感,对青霉素类、头孢菌素类、红霉素完全耐药。 结论NICU住院患儿肠道多重耐药菌定植情况比较严重,以产ESBLs肠杆菌、VRE为主,耐药现象严重。应重视日龄≥3 d新生儿肛拭子多重耐药菌的筛查,加强监测,避免多重耐药菌在医院内暴发流行。     

Drug resistance in fecal enterococci in Hong Kong

Our purpose was to estimate the rate of carriage of vancomycin-resistant enterococci (VRE) in hospitalized patients in a district hospital and in healthy subjects in the community in Hong Kong. Rectal swabs were collected from all patients admitted to the intensive care unit, and stool specimens were collected from all patients presenting with suspected antibiotic-associated diarrhea over a 2-month period. Stool specimens were also collected from healthy subjects in the community. Specimens were enriched and cultured on selective media for the isolation of enterococci. All isolates were identified, and their minimum inhibitory concentration for vancomycin was determined. Susceptibility to other antibiotics was investigated. Samples yielded 125 isolates of enterococci, the majority of isolates being Enterococcus faecalis (75) and E. faecium (35). Nine of 11 strains of E. gallinarum and 2 of 2 strains of E. casseliflavus isolated from hospitalized patients were intermediately resistant to vancomycin, but no strains highly resistant to vancomycin were isolated. Resistance to other drugs, including the fluoroquinolones, was present, and a high-level resistance to gentamicin and streptomycin was found in 37% and 46% of strains, respectively. Colonization with VRE remains low in Hong Kong. This result is supported by the low level of isolation of VRE from infections in the region and may be attributable to low levels of vancomycin use. High-level aminoglycoside resistance and fluoroquinolone resistance are common, and continued monitoring for VRE is suggested.     

高水平氨基糖苷耐药肠球菌的监测

目的了解高水平氨基糖苷耐药(HLAR)肠球菌的分离率,探讨青霉素类或糖肽类与氨基糖苷类药物合用对院内感染肠球菌的协同杀菌作用,为临床治疗肠球菌感染提供参考与指导。方法采用VITEK-AMS仪器对分离自临床标本的101株肠球菌进行氨苄西林、青霉素、万古霉素耐药性和高水平庆大霉素耐药(HLGR)及高水平链霉素耐药(HLSR)测定。结果101株肠球菌中,粪肠球菌、屎肠球菌、鸟肠球菌、母鸡肠球菌和耐久肠球菌菌株分别为71、13、8、7和2株。药敏测试结果显示肠球菌对氨苄西林、青霉素、万古霉素耐药分别为21、34和0株;HLGR和HLSR分别为79株和46株。结论院内感染肠球菌对抗菌药物存在严重耐药性,合理的抗菌药物治疗对高水平氨基糖苷耐药肠球菌感染患者的康复尤为重要。     

肠球菌耐药现状调查及抗感染用药探讨

目的了解肠球菌尤其是对万古霉素耐药肠球菌（ＶＲＥ）和庆大霉素高水平耐药（ＨＬＧＲ）肠球菌的耐药状况,指导临床合理用药。方法对北京５家教学医院感染标本中分离出的１６１４株肠球菌,分别进行纸片扩散法药敏试验和β内酰胺酶测试,并以“ＷＨＯＮＥＴ４”软件对试验数据进行分析处理。结果ＶＲＥ和ＨＬＧＲ肠球菌分别占肠球菌感染标本总数的３．４％和５２．６％,产β内酰胺酶的肠球菌占５．８％;对常用抗生素的耐药率,屎肠球菌明显高于粪肠球菌,ＨＬＧＲ株明显高于低耐株;万古霉素和高浓度庆大霉素多重耐药株检出率为０．９％。结论肠球菌对临床常用的８种抗生素以万古霉素最敏感。对不同特征肠球菌感染应采取不同的治疗方案。     

271株肠球菌属细菌的分布和耐药性分析

目的了解内蒙古鄂尔多斯市中心医院临床分离的肠球菌属细菌的分布情况及对各类抗菌药物的耐药性。方法使用VITEK 2 compact全自动细菌检测分析系统对2010年1月至2013年6月从临床标本中分离的271株肠球菌属细菌进行菌种鉴定和药敏试验,并用WHONET5．6软件对结果进行统计分析。结果271株肠球菌属细菌中,屎肠球菌137株（50．6％）,粪肠球菌80株（29．5％）,其他肠球菌54株（19．9％）。肠球菌属细菌主要分离自尿液69株（25．5％）、脓液40株（14．8o,4）、伤口等分泌物34株（12．5％）。粪肠球菌对万古霉素和利奈唑胺的耐药率分别为1．3％和1．5％;未检出呋喃妥因耐药株;对青霉素和氨苄西林的耐药率较低,分别为11．8％和2．6％;对高浓度庆大霉素和高浓度链霉素的耐药率分别为31．0％和22．9％。屎肠球菌的耐药率明显高于粪肠球菌,对万古霉素的耐药率为4．4％,未检出利奈唑胺耐药株,对呋喃妥因的耐药率为19．1％;对高浓度庆大霉素和高浓度链霉素的耐药率分别为44．8％和26．4％;但对四环素和奎奴普丁一达福普汀的耐药率低于粪肠球菌,分别为58．3％和0。结论屎肠球菌对抗菌药物的耐药率较粪肠球菌高;并已出现对万古霉素耐药株;其耐药性存在地区和菌种间差异,临床治疗应根据细菌药敏结果合理选用抗菌药物。     

Inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 56647) and five comparative antibiotics, used singly and in combination, against vancomycin-resistant and vancomycin-susceptible enterococci

The inhibitory and bactericidal effects of telithromycin (HMR 3647, RU 66647) were compared with those of gentamicin, ampicillin, erythromycin, azithromycin and vancomycin against 74 strains of enterococci (34 Enterococcus faecalis and 40 Enterococcus faecium) by agar dilution, broth dilution, time kill assays and postantibiotic effect (PAE). The telithromycin MIC(90) for vancomycin-sensitive (VSE) E. faecalis strains tested using the agar dilution method was 8 microg/ml. For a different group of VSE E. faecalis strains tested using the broth dilution method it was 0.06 microg/ml The telithromycin MIC(90)s for vancomycin-resistant (VRE) and VSE E. faecium strains, determined using the agar dilution method, were 4 and 8 microg/ml, respectively, while for a different set of VRE and VSE E. faecium strains tested using the broth macrodilution method, they were 32 and 16 microg/ml, respectively. Telithromycin MBC(90)s for E. faecalis were 4-6 tubes higher and for E. faecium 3-5 tubes higher, respectively, than the MIC(90)s. In time kill assays, telithromycin had bactericidal activity against only 1 of 7 E. faecium strains; for all other E. faecium and E. faecalis strains, only inhibitory activity was demonstrated. Neither synergy nor drug interference was observed when telithromycin was used in combination with ampicillin, vancomycin or gentamicin. At 10 times the MIC, the PAE of telithromycin against E. faecalis was 2.8 h, while for E. faecium it was 1.6 h. Telithromycin should be evaluated for therapy of enterococcal infections, including those caused by VRE organisms. However, because of the strain-to-strain variability in susceptibility to telithromycin, MIC determinations are important, especially for erythromycin-resistant strains.     

258株肠球菌耐药性分析及耐万古霉素基因检测

目的研究肠球菌的耐药率及耐万古霉素肠球菌(VRE)的耐药表型和基因型。方法按照美国临床和实验室标准化研究所(CLSI)2009年推荐的微量稀释法进行临床分离肠球菌对各类药物的最小抑菌浓度(MIC)检测,VRE进一步用E-test药敏试验确认;PCR法检测VRE的耐药基因。结果 2010年7月至2011年11月沈阳军区总医院共检出粪肠球菌95株,屎肠球菌163株。粪肠球菌对万古霉素、替考拉宁保持较高敏感度,对氨苄西林、青霉素、呋喃妥因三种抗菌药物敏感度也在65%以上,对其他抗菌药物敏感度低,统计期内未检出耐万古霉素粪肠球菌菌株。屎肠球菌对多数抗菌药物表现为耐药,对氯霉素敏感率为70%,对万古霉素、替考拉宁敏感度下降,为90.7%。期间检出15株VRE,其耐药表型为多重耐药,PCR扩增结果显示,15株万古霉素耐药屎肠球菌VanA基因扩增均为阳性,产物长度在700～1000bp之间,约783bp,符合预期;VanB、VanC引物扩增均阴性。15株万古霉素耐药屎肠球菌对多数抗菌药物耐药,仅对氯霉素、四环素相对敏感,对万古霉素MIC>256mg/L,对替考拉宁也表现为耐药。结论屎肠球菌耐药性高于粪肠球菌,VRE多为多重耐药,给临床治疗带来困难,医院应加强对其预防监测。     

Comparative in vitro activity of quinupristin/dalfopristin against multidrug resistant Enterococcus faecium

The in vitro susceptibilities of 82 strains of vancomycin resistant Enterococcus faecium (VREF), (49 vanA and 33 vanB) from over 13 hospitals in Europe and United States were studied. The MIC for several antibiotics showed high levels of resistance to vancomycin, ampicillin, gentamicin, and imipenem. All VREF strains were highly susceptible to quinupristin/dalfopristin with a MIC 90% of 0.5 μg/ml for both vanA and vanB phenotypes. Time-kill and synergy studies of VREF for quinupristin/dalfopristin alone and quinupristin/dalfopristin in combination with several antibiotics (ampicillin, gentamicin, ciprofloxacin, rifampin and novobiocin) did not show bactericidal activity. In induction experiments using SF6550, (VREF, a vanA strain), quinupristin/dalfopristin showed a delay in the expression of vancomycin resistance by 2.5 hours. The results of this study show quinupristin/dalfopristin to have excellent in vitro activity versus multiple resistant E. faecium.     

2007-2012年浙江萧山医院尿路感染患者的肠球菌分布及耐药性分析

目的 调查从尿路感染患者分离的肠球菌的菌种、临床分布及耐药性,为临床合理选用抗生素提供依据。方法 尿培养采用经典型浸片Uricult,ATB-Expression细菌分析系统进行鉴定和药敏试验;所有资料采用Whonet 5.6软件进行回顾性分析。结果 分离肠球菌238株,主要为粪肠球菌122株（51.3%）和屎肠球菌95株（39.9%）;菌株主要来源列前2位的是内科（38.2%）和泌尿外科（21.0%）;耐药率较高的是红霉素（86.5%）、利福平（75.7%）和四环素（66.4%）;较低的是呋喃妥因（19.7%）、万古霉素（9.6%）和利奈唑胺（0.0%）;粪肠球菌对利福平、红霉素、奎奴普丁/达福普汀和四环素的耐药率较高,均76.5%,万古霉素耐药率0.9%;屎肠球菌对氨苄西林等8种药物耐药率75.8%,万古霉素耐药率4.3%。粪肠球菌对所测试抗生素耐药率仅有四环素、奎奴普丁/达福普汀高于屎肠球菌,其余低于屎肠球菌;利福平、万古霉素和利奈唑胺耐药率在二者间差异无统计学意义。2007年与2012年相比,青霉素、氨苄西林等药物耐药率上升,而环丙沙星、四环素等下降。结论 肠球菌是引起尿路感染的重要病原菌,以粪肠球菌和屎肠球菌为主,不同种类肠球菌耐药率差别较大,加强细菌培养和定期分析其耐药性,有助于提高临床治愈率及合理用药水平。     

European survey of vancomycin-resistant enterococci in at-risk hospital wards and in vitro susceptibility testing of ramoplanin against these isolates

A survey in eight European countries, including 13 hospitals, of vancomycin-resistant enterococci (VRE) in at-risk hospital wards (such as the ICU and the haematology ward) was performed in 2001, and the in vitro susceptibility of the isolates ramoplanin and other drugs was tested. A total of 1314 non-duplicate clinical enterococcal isolates were collected, and 38 (2.9%) were vancomycin resistant: 27 Enterococcus faecium and 11 Enterococcus faecalis; 35 VanA and three VanB phenotypes. Rates of VRE among clinical enterococcal isolates varied between 0 and 1.7% for the participating countries, except the UK (10.4%) and Italy (19.6%). One hundred and twenty-three (3.5%) VRE were found among 3499 stool samples tested for the presence of these organisms: 111 (3.2%) E. faecium and 12 (0.3%) E. faecalis; 114 (3.3%) VanA and nine (0.3%) VanB phenotypes. Rates of intestinal colonization with VRE varied between 0 and 1.2% for the participating countries, except Italy (7.5%) and the UK (32.6%). In vitro susceptibility testing showed that the Italian and UK VRE are multi-resistant (including resistance to ampicillin and high-level resistance to gentamicin and streptomycin), and that ramoplanin was active against all strains of VRE, with an MIC90 of 0.5 mg/L for clinical isolates. Pulsed-field gel electrophoresis showed that the high prevalence of VRE in the Italian and UK centres was related to the monoclonal emergence and spread of three centre-specific clones. This survey suggests that in some centres in Europe, a similar situation may be encountered to that in the USA (monoclonal spread of multi-resistant VRE in at-risk wards).     

Susceptibility patterns of enterococci causing infections

Enterococci are among the common organisms associated with hospital-acquired infections. We examined in vitro activities of different antibiotics to 103 enterococcal isolates. Minimal inhibitory concentrations (MICs) of penicillin G, ampicillin, gentamicin, ciprofloxacin, ofloxacin, levofloxacin, grepafloxacin, trovafloxacin and gemifloxacin were determined by broth microdilution testing method. Among the isolates 71 (69%) were identified as E. faecalis and 32 (31%) as E. faecium. While over 75% of E. faecium isolates were resistant to penicillin and ampicillin, approximately 25% of E. faecalis isolates were resistant to penicillin and ampicillin. None of the E. faecalis and E. faecium isolates were resistant to vancomycin. While 17 (52%) of E. faecium isolates exhibited high-level gentamicin resistance (HLGR), high level streptomycin resistance (HLSR) was detected in 24 (74%) of the isolates. In contrast, HLGR and HLSR rates for E. faecalis were 14 (20%) and 22 (31%), respectively. Both HLGR and HLSR were detected with higher frequency in ampicillin resistant isolates. Among fluoroquinolones, gemifloxacin and trovafloxacin were the most potent antibiotics tested. There was no increase in MIC90 values of the fluoroquinolones in ampicillin resistant isolates in comparison with ampicillin susceptible isolates. Our data suggest newer fluoroquinolones would be good alternative agents to use especially for combination drug therapy where enterococci with ampicillin resistance and HLAR are prevalent.     

耐万古霉素肠球菌表型检测及基因分型

目的 研究对万古霉素耐药或中介的肠球菌株的表型和基因型，以了解本院耐万古霉素肠球菌（VRE）的流行状况，指导临床合理用药。方法 收集200株临床分离的肠球菌株，用琼脂筛选法筛选VRE，并分别用E test和多重PCR检测和分析对万古霉素耐药或中介肠球菌株的表型和基因型。结果 共检出10株对万古霉素耐药或中介的肠球菌株，其中5株为天然耐万古霉素肠球菌。基因型分析的结果为1株van A型，4株van C1型，3株van C2型，2株基因型不明。结论 已发现5株VRE（1株VAN A型），提示临床上须合理使用抗生素，以防止VRE等多重耐药细菌的爆发流行。     

Novel antibiotic regimens against Enterococcus faecium resistant to ampicillin, vancomycin, and gentamicin.

Enterococci have emerged as significant nosocomial pathogens. Enterococci with resistance to commonly used antibiotics are appearing more frequently. We encountered at our institution several infections caused by Enterococcus faecium with high-level resistance to ampicillin, vancomycin, and gentamicin. The optimal antibiotic therapy for serious infections with unusually resistant enterococci has not been established. Using time-kill studies, we tested the effectiveness of various antibiotic combinations against 15 isolates of multidrug-resistant enterococci. No antibiotic was consistently effective when used alone. The combination of ampicillin plus ciprofloxacin was bactericidal for the 12 isolates for which the ciprofloxacin MIC was < or = 8 micrograms/ml. The combination of ciprofloxacin plus novobiocin also demonstrated activity against these isolates. No combination was found to be bactericidal for the remaining three isolates, which were highly ciprofloxacin resistant. These antibiotic combinations may be important for the future treatment of serious infections caused by these resistant pathogens.     

The resistance ofEscherichia coli strains isolated from community-acquired urinary tract infections

Urinary tract infections (UTIs) are the most common infections caused byEscherichia coli. Most recent research demonstrates that antibiotic resistance has reached a critical point throughout the world, as increased use of antibiotics among nonhospitalized patients encourages the growth of drug-resistant pathogens among that population. The goal of this study was to determine the antimicrobial drug resistance ofE coli strains isolated from community-acquired UTIs in 5 different regions in Turkey. The minimum inhibitory concentrations of ciprofloxacin, gentamicin, sulfamethoxazole, trimethoprim, trimethoprim-sulfamethoxazole, and ampicillin and forE coli were determined with the agar dilution method. Among the 480 strains isolated, 8.3% were resistant to ciprofloxacin, 3.3% to gentamicin, 35.4% to sulfamethoxazole, 33.3% to trimethoprim, 27.9% to trimethoprim-sulfamethoxazole, and 40.8% to ampicillin. These results show that the antibiotics currently most effective againstE coli are ciprofloxacin and gentamicin. Local epidemiologic trends should be considered when prescribing antibacterial therapy. More research in bacterial gene mapping will be necessary to elucidate the influence of regional antimicrobial drug use and resistance in epidemiologic trends among the general population.     

Molecular characterization of multidrug-resistant Enterococcus spp. from poultry and dairy farms: detection of virulence and vancomycin resistance gene markers by PCR

Thirty multidrug-resistant Enterococcus spp. strains, including two from the milk of cows with mastitis, nine from chicken litter and 19 from turkey litter, were isolated. Twenty-five were identified by biochemical methods as E. gallinarum and five as E. faecalis. Most of the isolates were resistant to vancomycin, gentamicin, streptomycin, tetracycline, erythromycin, bacitracin, kanamycin and nalidixic acid but sensitive to ciprofloxacin, sulfamethoxazole, chloramphenicol, ampicillin and ofloxacin. Attempts were made by partial amplification of the gene sequences to detect the vancomycin resistance markers vanA (734-bp), vanB (420-bp), vanC1 (531-bp), and vanC2-C3 (673-bp); virulence markers cylA (427-bp) and cylB (225-bp) for enterococcal cytolysin and a biofilm-forming surface protein (Esp). Individual and multiplex-PCR assays for vancomycin resistance markers revealed the vanC1 gene in 22 E. gallinarum strains. None of the remaining isolates including five E. faecalis strains (MIC=2 microg ml(-1)) and three E. gallinarum strains (MIC=8 microg ml(-1)) had any of the van genes tested. Analysis by pulsed-field gel electrophoresis (PFGE) and a comparison of smaI banding profiles showed 11 different patterns. Probing with a DIG-labeled vanC1 PCR product indicated a common 38.0 kb SmaI DNA fragment in all the E. gallinarum strains harboring the vanC1 gene. The genes cylA and cylB were detected only in one clinical E. gallinarum isolate and two quality control clinical strains of E. faecalis (ATCC 51299 and 29212). None of the virulence factors were found in milk or poultry isolates. Intermediate level resistance to vancomycin in enterococci from the US animal farms was predominantly due to the presence of vanC1 gene.     

In vitro activity of the trinem sanfetrinem (GV104326) against gram-positive organisms.

The in vitro activity of the trinem sanfetrinem (formerly GV104326) (GV) was compared with that of vancomycin, ampicillin, and/or nafcillin against 287 gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and multiresistant enterococci, by the agar and microbroth dilution methods. GV demonstrated 2 to 16 times more activity than ampicillin and nafcillin against the majority of these organisms. The MIC range of GV was 16 to 64 micrograms/ml for 19 Enterococcus faecium strains that were highly resistant to ampicillin (ampicillin MIC range, 64 to 512 micrograms/ml) and vancomycin resistant and 0.25 to 32 micrograms/ml for resistant Rhodococcus spp. Similar activities (+/-1 dilution) were observed by either the agar or the broth microdilution method. GV demonstrated bactericidal activity against a beta-lactamase-producing Enterococcus faecalis strain and against two methicillin-susceptible Staphylococcus aureus strains in 10(5)-CFU/ml inocula. Synergy between GV and gentamicin was observed against an E. faecalis strain that lacked high-level gentamicin resistance. The activity of GV suggests this compound warrants further study.     

Bactericidal activities of peptide antibiotics against multidrug-resistant Enterococcus faecium.

Multidrug-resistant Enterococcus faecium has emerged as a serious pathogen for which no effective therapy has been established. In this report, we describe the activities of two peptide antibiotics, ramoplanin and daptomycin, against 15 isolates of E. faecium resistant to vancomycin, ampicillin, and aminoglycosides using time-kill experiments. Both antibiotics were rapidly bactericidal when tested in broth; however, the addition of 50% serum resulted in significant regrowth. The combination of ampicillin with either ramoplanin or daptomycin largely prevented this regrowth. These peptide antibiotics showed good activity against these pathogens. While the development of daptomycin has been halted, ramoplanin may hold promise for the therapy of multidrug-resistant E. faecium, especially when combined with ampicillin.     

A comparison of high-level aminoglycoside resistance in vancomycin-sensitive and vancomycin-resistant Enterococcus species

The aim of this study was to investigate whether there was a significant difference in high-level aminoglycoside resistance (HLAR) between vancomycin-sensitive enterococci (VSE) and vancomycin-resistant enterococci (VRE). Vancomycin resistance was determined in 116 Enterococcus isolates using brain-heart infusion agar containing 6 micrograms/ml vancomycin. HLAR was determined by both standard agar screening and disk diffusion methods. Streptomycin and gentamicin were used as predictors of HLAR. Vancomycin resistance and HLAR were found in 17 (14.7%) and 41 (35.3%) of the Enterococcus strains, respectively. HLAR was found in 11 of 17 VRE and 30 of 98 VSE strains. HLAR in VRE strains was significantly higher than in VSE. More enterococcal strains were found to be resistant to both gentamicin and streptomycin (29) than to gentamicin (one) or streptomycin (11) alone. The HLAR rate in VRE was two-fold higher than in VSE. The synergistic bactericidal effect of aminoglycosides and beta-lactam or glycopeptide antibiotics is lost if there is high-level resistance to aminoglycosides.     

Development of new antibiotic resistance in methicillin-resistant but not methicillin-susceptible Staphylococcus aureus.

The frequency of infections caused by multidrug-resistant Staphylococcus aureus continues to increase while the numbers of alternative therapeutic agents remain limited. To investigate the changing patterns of in-vitro susceptibility of S. aureus to 16 antibiotics, 190 clinical isolates from two different years were studied. The MICs of methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains isolated in 1987 were compared with those of similar numbers of strains isolated in 1989. For MRSA > or = 90% of isolates from both years were resistant to clindamycin, gentamicin and erythromycin. These strains remained highly susceptible to vancomycin (100%), minocycline (90%) and rifampicin (100%). The greatest increase in resistance was observed for ofloxacin (2% in 1987 vs 62% in 1989); cross-resistance to all of the quinolones tested was demonstrated. MSSA strains remained susceptible to vancomycin (100%), minocycline (98%), rifampicin (100%), clindamycin (90%), gentamicin (90%) and ciprofloxacin (98%). It is concluded that methicillin susceptibility is a useful marker for selecting potential agents for the treatment of infections caused by S. aureus. A combination of minocycline and rifampicin may be a useful alternative to vancomycin for treating MRSA infections.